Method of granulating powder and apparatus for it

ABSTRACT

The present invention is intended for granulation of powder comprising the steps of mixing a powder and a mist of binder by fluidizing air flow, collecting the mixture of the powder and the binder on a filter surface thereby forming a powder layer thereon, peeling off the powder layer from the filter surface thereby crushing the powder layer into pieces, returning the crushed fragments into the fluidizing air flow and mixing them with the mist of binder again, repeating the steps until the desired granule is obtained.

BACKGROUND OF THE INVENTION

The present invention relates to a method of granulating powder and anapparatus for granulating powder and, more specifically, to a method ofgranulating powder applied in the manufacture of granulated or powderyproducts such as pharmaceuticals, food, agricultural chemicals,ceramics, etc. (hereinafter referred to as "granule" or "granulatedproduct" in some cases) and an apparatus for granulating powder.

Fine powder the particle diameter of which is several μm or under isgenerally light and easily dispersed although there is also heavy powdersuch as metallic powder, and the fine particles which fly up have strongadhesion to the inner face a of container, etc. of a fluidized bedgranulating apparatus.

Moreover, such light fine powder is poor in fluidity and cannot form thenecessary fluidized bed for performing fluidized bed granulation, forexample. This is because all of the powder cannot be moved if thefluidizing air capacity for fluidized bed granulation is small but, asthe air capacity is gradually increased, the powder suddenly flies uplike smoke, and it is impossible to find any proper air capacity forfluidization.

Also, the flied-up light fine powder can adhere to the inner face of thecontainer, etc. of the fluidized bed granulating apparatus and graduallyaccumulates there. This deposition is not easily removed. So the lightfine powder cannot be mixed, much less granulated in fluidized bedgranulating apparatuses.

Furthermore, such light fine powder, which has a strong flocculatingperformance in addition to the abovementioned nature, often forms aflocculated lump consisting of hundreds to thousands of primaryparticles, and it is impossible to coat all of the primary particleswith a binder because the flocculated lump cannot be dispersed intoindividual primary particles with the various granulating methodscurrently put into practice.

Therefore, granules formed by this method has the problem of beingeasily destroyed because it contains flocculated lumps without binderinside.

In addition, in the case where compression moldings (tablets) are madeby using this granule containing flocculated lumps without binderinside, the flocculated lumps inside the granule change, under pressure,into hard lumps which are not easily dispersed at the time ofdissolution. This is due to the absence, between primary particles, ofany binder which serves as a dispersing agent at the time ofdissolution, and such phenomenon spoils the effect or meaning ofpulverization of raw material, etc. made for any specific purpose suchas improvement of solubility, for example.

As described above, it has so far been considered impossible to performfluidized bed granulation of light fine powders or to perform fluidizedbed granulation while coating individual particles constitutingflocculated lumps which consists of light fine powder with a binder.

SUMMARY OF THE INVENTION

The object of the present invention is to provide a method enablinggranulation of powder such as light fine powder, etc., and morespecifically granulation made while coating individual primary particlesconstituting flocculated lump which consists of light fine powder with abinder, and an apparatus for it.

To achieve the above-mentioned object, the method of granulating powderaccording to the present invention is a method of granulating powdercomprising the steps of; mixing a powder and a mist of binder byfluidizing air flow, collecting the mixture of the powder and the binderon a filter surface thereby forming a powder layer thereon, peeling offthe powder layer from the filter surface thereby crushing the powderlayer into pieces, returning the crushed fragments into the fluidizingair flow and mixing them with the mist of binder again, repeating thesteps until the desired granule is obtained.

In this case, if a binder is spotted on the surface of flocculated lumpsformed with flocculation of a large number of primary particles and theflocculated lumps are collected on a filter and, after point combining,crushed from a portion not combined with the binder, flocculated lumpsare formed on the surface of which appear the primary particles whichhave so far been positioned inside the flocculated lumps. By returningthose flocculated lumps into the powder and repeating the granulatingand crushing operations, secondary particles which are coated with thebinder on all the individual primary particles are obtained.

Granulation can be made by incorporating the method of granulatingpowder according to the present invention in the conventionalgranulating method utilizing air flow. Here, granulating methodutilizing air flow includes such granulating methods as spouted bedgranulating method, roll granulating method, complex granulating method,etc. in addition to fluidized bed granulating method.

Moreover, the structure of the granulating apparatus according to thepresent invention can be incorporated in said conventional generalapparatus for granulating powder by using air flow. Its construction ischaracterized in that it disposes, on the inner circumferential face ofa closable main body container, a filter for forming powder layerconsisting of powder and binder in a way to form a space against theinner circumferential face of the main body container, and a backwashand exhaust mechanism which selectively performs backwash or exhaustthrough this filter.

Furthermore, apart from said general granulating apparatus, theapparatus according to the present invention is characterized in that ithas the central part at the top face of the main body containerdepressed and disposes a spray nozzle at the center of that part,disposes a filter for forming powder layer consisting of powder andbinder on the top face around it in a way to form a space against thetop face, and disposes a backwash and exhaust mechanism whichselectively performs backwash or exhaust through this filter.

Still more, it is possible to divide said space into a plural number ofzones by such way as splitting it into zones disposed one upon anotherin the vertical direction of the main body container for example, in away to form a plural number of ring-shaped zones, suck and hold thefilter by performing exhaust through the filter in zones other than thezone where backwash is being made and make backwash of the filter whilekeeping it at prescribed position, for effective backwashing.

By the method and apparatus according to the present invention, itbecomes possible to not only perform granulation with the followingfeatures but also effectively perform granulation process of powderincluding manufacture of powder by spray-dry.

(1) Enables granulation of light fine powder of a particle size nolarger than several μm which may fly up without forming any fluidizedbed.

(2) Enables manufacture of granulated products with excellent solubilityand strong binding force, thanks to the possibility of obtaining granuleconsisting of primary particles which are coated with a binder aboutuniformly on the surface.

(3) Enables uniform granulation of all powdery materials withoutnon-granulated powder in granulated products.

(4) Enables granulation in uniform size without coarse granules ingranulated products.

(5) Enables granulation in a state of low water content when granulatinga powdery material which is liable to cause hydrolysis.

(6) Enables manufacture of granulated products with uniform composition,when granulating several different kinds of easily classifiable powderymaterials.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a front vertical section showing a conventional fluidized bedgranulating apparatus.

FIG. 2 is a front vertical section showing an example of an apparatusfor granulating powder according to the present invention.

FIG. 3 is a front vertical section showing a modified example of theapparatus for granulating powder according to the present invention.

FIG. 4 is a schematic diagram showing the fluidizing and blendingprocess of powder in granulating step 1, of a method of granulatingpowder according to the present invention.

FIG. 5 is a schematic diagram showing a deflocculating process of powderin the granulating step II, of the method of granulating powderaccording to the present invention.

FIG. 6 is a schematic diagram showing the initial granulating process ofpowder in granulating step III, of the method of granulating powderaccording to the present invention.

FIG. 7 is a schematic diagram showing the intermediate granulatingprocess of powder in granulating step IV, of the method of granulatingpowder according to the present invention.

FIG. 8 is a schematic diagram showing the regular granulating process ofpowder in granulating step V, of the method of granulating powderaccording to the present invention.

FIG. 9 is a schematic diagram showing a growing process of particlesfrom initial granulating process to regular granulating process of themethod of granulating powder according to the present invention.

FIG. 10 is a vertical section showing an apparatus for granulating on afilter with a spray-dry function.

FIG. 11 is a schematic diagram showing movement of the powder duringbackwashing of the apparatus for granulating on a filter with thespray-dry function in FIG. 10.

DETAILED DESCRIPTION OF THE INVENTION

The powder forming the subject of the present invention is a light finepowder having properties of flying up without forming any fluidized bedand of being caught by a filter and other similar powders. Suchproperties of flying up without forming any fluidized bed and of beingcaught by a filter have been positively utilized to invent a method ofgranulating light fine powder up to a size enabling formation of afluidized bed.

This new granulating method is a method which includes blowing up lightfine powder with a fluidizing air flow, spraying a binder on theblown-up powder, mixing the powder and the mist of binder with afluidizing air flow and collecting the mixture on a filter. Therebyforming a high-density powder layer on the filter in such a way as tomutually combine the particles inside this high-density powder layer.This layer is peeled off from the filter and crushed into pieces withthe backwashing of this powder layer. The crushed fragments are returnedinto the fluidizing powder, flown up, mixed with the mist again andcollected on a filter. These operations are repeated to finely granulatethe powder.

The apparatus used for performing granulation by this method will beexplained hereafter by comparison with a conventional apparatus.

The apparatus of this invention, as shown in FIG. 2, includes a sealedmain body container 1, and a filter 3 which is disposed apart from theinside wall 1a of the main body container 1 so as to form anintermediate exhaust chamber 8. A top air supplying chamber 2 is mountedat the top of the main body container 1, and a product container 10 isdisposed at the bottom of the main body container 1. A screen plate 6 isdisposed at the bottom of the product container 10, a bottom airsupplying chamber 7 is disposed below the product container 10, and aspray nozzle 9 is disposed at the top-center of the main body container1, which sprays a binder therein.

A fluidizing air is supplied from the bottom air supplying chamber 7 andthrough the screen plate 6 thereby fluidizing and mixing powder insideof the main body container 1.

Also, this apparatus is constructed in such a way that the air flowsupplied from the top air supplying chamber 2 and the bottom airsupplying chamber 7 into the main body container 1 passes through thefilter 3 and is discharged to the outside of the main body container 1.

The filter 3 is constructed such that it will allow the passage of air,etc. but it will prevent the passage of light fine powder. The filter isa double-layer structure having an inner filter 3a of woven fabric ofTetoron disposed on the inner side (center side of the main bodycontainer 1) and an outer filter 3b of non-woven fabric of Tetoron. Atleast the outer filter 3b is divided, as described later, into a firstfilter 31, second filter 32, a third filter 33, a fourth filter 34 and afifth filter 35 in this order from the top.

This apparatus is therefore constructed so as to form a plurality ofzones with the respective filters 31, 32, 33, 34, 35 and the wall 1a andthe partition ring 1b of the main body container 1. This arrangementforms ring-shaped intermediate exhaust chambers 81, 82, 83, 84, 85 whichmake it possible to selectively perform exhaust or backwash operationsindependently of each other by means of an exhaust mechanism 4 and abackwash mechanism 5 connected to the respective intermediate exhaustchambers 81, 82, 83, 84, 85.

In this case, the intermediate exhaust chambers 81, 82, 83, 84, 85 areconnected to the exhaust mechanism 4 through exhaust valves 41, 42, 43,44, 45 and to the backwash mechanism 5 through backwash valves 51, 52,53, 54, 55 respectively.

Also, the exhaust valves 41, 42, 43, 44, 45 and the backwash valves 51,52, 53, 54, 55 are constructed in such a way that, while either one ofthe valves is open to one intermediate exhaust chamber, the other valveis closed.

Moreover, the outer filter 3b is joined with the partition ring 1b atboth ends of the respective filters 31, 32, 33, 34, 35 while the innerfilter 3a is connected to the partition rings 1b at the top end of thefirst filter 31 and at the bottom end of the fifth filter 35.

As the exhaust mechanism 4 and the backwash mechanism 5 operate toexhaust and backwash the filter 3, the filter 3 can suck material at onepart while the sucked material peeled and crushed at another part.Namely, as the exhaust valves 41, 42, 43, 44, 45 are opened and thebackwash valves 51, 52, 53, 54, 55 are closed, the exhaust mechanism 4performs exhaust operations from inside the main body container 1through the filter 3 making it possible for the filter 3 to suckmaterial and, in the opposite case, the backwash mechanism 5 feedscompressed air for backwashing material, which has been caught by thefilter 3, into the main body container 1, enabling peeling of thematerial from the filter 3.

In this case, the backwash valves 51, 52, 53, 54, 55 are usually openedsequentially from top to bottom (they can also be opened from bottom totop or in any desired order) to backwash the filter 3 and peel thematerial on the filter 3.

The opening time of the backwash valves 51, 52, 53, 54, 55 can be setshort because this peeling of substance can be completed in a shorttime.

Next, explanation will be given on the motion of exhaust valves andbackwash valves during operation. First, basically the five exhaustvalves 41, 42, 43, 44, 45 are left open. Then a first exhaust valve isclosed and the corresponding backwash valve is opened for an instant,for one second for example, and closed immediately after that, and theexhaust valve is opened. After that, this operation is repeated in a setsequence, from top to bottom for example.

As described above, since at least 4 of the 5 exhaust valves 41, 42, 43,44, 45 are left open, it is possible to not only perform exhaust byutilizing at least 80% of the surface area of the filter 3 but also tosuck and hold the inner filter 3a, which is connected to the partitionring 1b only at the top end and the bottom end and perform backwashsmoothly.

On the other hand, in a conventional fluidized bed granulatingapparatus, a filter 3 is disposed at the top of the container, as shownin FIG. 1. In the case where this filter is disposed in a flat shape insuch a way as to cover the inner circumferential face of the main bodycontainer 1, as in the apparatus which performs fluidized bedgranulation of light fine powder according to the present inventionindicated in FIG. 2, it becomes easy to catch the light fine powderflying up from the product container 10, and the return of collectedpowder to the product container 10 after dusting it off by backwashingalso becomes easier because of the short distance.

Moreover, by disposing the filter 3 in such a way as to cover the innercircumferential face of the main body container 1, a solution to theproblem of adhesion of powder to the inner face of the main bodycontainer 1 is provided.

Furthermore, with the use of a flat filter without pleats, etc. for thefilter 3, peeling of the powder layer becomes easier.

The binder nozzle 9 will be a top spray type and will be mounted on thetop face of the main body container 1. The height of nozzle 9, whichvaries depending on the nature of the powder and the binder as well asthe apparatus size, will be normally set at about double the nozzleheight in a conventional apparatus.

Next, explanation will be given on countermeasures against flocculatedlumps which has been considered as a big problem in the granulation oflight fine powder, namely the method of coating binder on each piece ofthe primary particles while loosening the flocculated lump.

Destruction of flocculated lumps is impossible even with fluidizationand agitation of the powder with a forced air flow or an agitating bladeby using a conventional fluidized bed granulating apparatus, a spoutedbed granulating apparatus, a roll granulating apparatus, or a complexgranulating apparatus, and instead the lump may even grow larger in somecases.

Therefore, a method of destroying the flocculated lump by using a bindermist has been invented.

First, a volume of the binder mist which is smaller than normal isprovided on the surface of the flocculated lump. And, as the flocculatedlumps are collected on the filter together with other powder and bindermist, thus forming a high-density powder layer on the filter, the bindermist gets in the state of existing here and there on individualparticles inside the powder layer, and only the portion with such spotsproduces a combination.

Next, in the case where the powder layer is peeled from the filter andcrushed into pieces, the crushing of the powder layer takes place withrespect to a portion which is not combined with binder, in other wordsfrom a flocculated portion.

This means that the first flocculated lump has been crushed from insideand, by repetition of this operation, it becomes possible to granulatethe first flocculated lump while crushing it and coat the individualparticles of that lump with binder while loosening the flocculation.

Therefore, by the combined use of said new granulating method and themethod of loosening flocculation with the mechanism of apparatus shownin FIG. 2, it becomes possible to granulate flocculated lumps consistingof light fine powder to a size which will enable the formation of afluidized bed from primary particles and, with continued fluidized bedgranulation, obtain granules of good quality.

Next, FIG. 3 illustrates a modified example of the apparatus forgranulating powder as shown in FIG. 2.

This apparatus is constructed in such a way that the first filter 31 ofthe powder granulating apparatus indicated in FIG. 2 is extended up tothe corner at the top of the main body container 1, in other words tothe connecting part between the top face of the main body container 1and the wall la so as to form a top filter 30. Also, in the same way asthe other filters 32, 33, 34, 35, demarcation is made with the wall la,the top face of the main body container 1 and the partition ring 1b tothereby form a ring-shaped intermediate exhaust chamber 80. This makesit possible to selectively perform exhaust or backwash operationsindependently of the other filters 31, 32, 33, 34, 35 by means of anexhaust mechanism 4 and a backwash mechanism 5 connected to theintermediate exhaust chamber 80.

In this case, the intermediate exhaust chamber 80 is connected to theexhaust mechanism 4 through exhaust valve 40 and to the backwashmechanism 5 through backwash valve 50 respectively.

Also, the exhaust valves 40, 41, 42, 43, 44, 45 and the backwash valves50, 51, 52, 53, 54, 55 are constructed in such a way that, while eitherone of the valves is open to one intermediate exhaust chamber, the othervalve is closed.

Moreover, the apparatus is constructed in such a way that the outerfilter 3b is joined with the partition ring 1b at both ends of therespective filters 30, 31, 32, 33, 34, 35 while the inner filter 3a isjoined with the partition ring 1b at the top end of the top filter 30and at the bottom end of the fifth filter 35.

This makes it possible to not only prevent matter from adhering to thecorner at the top of the main body container 1, namely to the connectingpart between the top face of the main body container 1 and the wall la,but also to suck and peel matter which has collected at the top filter30, thus enabling effective granulation.

Other constructions and operations of the apparatus illustrated in FIG.3 are the same as those of the apparatus shown in FIG. 2.

The process of fluidized bed granulation of light fine powder, using theapparatus of FIG. 2 or FIG. 3, will be explained hereafter withreference to FIG. 4 to FIG. 8.

FIG. 4 is a schematic diagram showing the fluidizing and blendingprocess of powder in granulating step 1.

As shown in FIG. 4, the light fine powder in the product container 10flies up at the moment when fluidizing air flow is fed into the mainbody container 1 from the bottom of the product container 10. Thepowder, carried by the fluidizing air flow, hits against the filter 3disposed on the inner circumferential face of the main body container,and is caught by the filter 3.

The light fine powder forms a filtration layer, and it is possible evenfor a general filter 3 made of woven fabric of Tetoron, etc. to collectfine powder in units of a submicron order.

Even after formation of filtration layer, light fine powder continueshitting against the filter 3 and sticking to the surface of the filter3. The light fine powder adhering to the surface of the filter 3 ispeeled from the filter 3 and dropped to the bottom of the productcontainer 10 as flocculated lumps with backwashing which is performed inregular cycles.

The flocculated lumps which are pulverized as a result of collisionsamong the flocculated lumps themselves, etc., fly up again by riding onthe fluidizing air flow introduced into the main body container 1 fromthe bottom of the product container 10, and stick to the surface of thefilter 3.

This operation is repeated and, as a result, even light fine powderwhich cannot form a fluidized bed in the main body container 1 comes tobe fluidized and mixed eventually by going to and from the surface ofthe filter 3 and the bottom of the product container 10. In the case ofan easily classifiable powder, though it is divided into a part thatforms a fluidized bed at the bottom and the other part that flies up thepolarized two (2) different kinds of powder are mixed uniformly again inthe granulation process to be described later if they are well mixed,and do not present any particular problem in the case of ordinarypowder.

FIG. 5 is a schematic diagram showing the deflocculating process ofpowder in the granulating step 11.

A binder is sprayed from the nozzle 9 onto the flocculated lump formedin the granulating step 1. In case the whole surface of the flocculatedlumps are coated with binder, a sudden granulation will occur. Toprevent this phenomenon, it is preferable to limit the amount of thebinder to within 40 to 60% of hot air drying capacity and to spray mistwith a diameter less 10 μm.

Moreover, the volume of mist advancing air fed from the binder nozzle 9is adjusted in such a way that the spray travel of the binder mist comesfrom the top or upper end of the product container 10. This avoids thephenomenon of self drying of the binder mist by making it reach thefilter quickly, and thus prevents drying and pulverization of heavyflocculated lumps fluidizing at the lower part of the container 10.

As a result, the binder mist is spotted on the surface of theflocculated lumps. The flocculated lumps are collected with other powderand the binder mist on the filter 3 so as to form a powder layer, inwhich the particles of the binder mist exist in spots, where the bindingtakes place.

Next, the powder layer on the filter 3 is peeled and crushed into pieceswith backwashing which is performed in regular cycles. At that time, thepowder layer is destroyed, not at the portions that adhere with a strongbinding force, but at the flocculated portions which are held with weakbinding forces. The crushed layer drops in the product container 10.

Fragments of the powder layer are further dried in the product container10 which causes pulverization thereof, but the adhering particles arenot destroyed but ride up on the fluidizing air flow as flocculatedlumps containing adhering particles.

The surfaces of the flocculated lumps are spotted again with the bindermist, to form a powder layer on the filter 3 in the same way as beforeand, inside the formed powder layer, the newly sprayed binder mist ispresent in spots which, cause new combinations in those portions only.

As this operation is repeated, the binder mist is eventually coated onall primary particles because priority of coating is given to primaryparticles which have not yet been coated with the binder mist.

Also, adhering particles also increase gradually to generate secondaryparticles consisting of tens of primary particles. However, since thisprocess is that of granulation in a dry state and the secondaryparticles lack water content and plasticity, continued granulation inthis state may produce granules of high porosity, having small bulkdensity and weak strength. Therefore, in order to give the secondaryparticles the necessary plasticity, following is the next step of theprimary granulation process in which an increased volume of binder sprayis supplied.

FIG. 6 is a schematic diagram showing the initial granulating process ofpowder in granulating step III.

In the initial granulation process, the volume of binder sprayed fromthe binder nozzle 9 is increased to a volume corresponding to 90 to 95%of the hot air drying capacity for spraying on the secondary particles.

The secondary particles become soft as they get wet by sufficientlycontaining the binder mist. And, these secondary particles rise up onthe fluidizing air flow together with other dry and hard secondaryparticles and binder mist, and are collected on the filter 3 to form ahigh-density powder layer.

Inside this powder layer are produced a portion in which soft secondaryparticles, wet with binder mist, are combined with a portion whichremains in a dry and hard state.

In FIG. 6, secondary particles which are wet by containing a sufficientamount of binder, are represented by thick circles.

Next, by backwashing, the powder layer is destroyed, thereby generatingprimary granules.

The primary granules drop because they are wet and heavy with binder anddue to mutual combining of secondary particles, or drop on the screenplate 6 of the product container 10, were they hit against and crush andpulverize residual flocculated lumps, while the primary granulesthemselves are dried on the screen plate 6 of the product container 10and partially pulverized.

In the initial granulating process of powder in granulating step 111,granulation progresses on the filter 3 though no fluidized bed isformed, and the particle diameter of the primary granules graduallyincreases (this granulation is specially called & "granulation on thefilter" as distinguished from fluidized bed granulation).

FIG. 7 is a schematic diagram showing the intermediate granulatingprocess of powder in granulating step IV.

As granulation on the filter is repeatedly performed by the initialgranulating process of powder in the granulating step III shown in FIG.6, the operation gets into an intermediate granulating process of powderin the granulating step IV shown in FIG. 7.

In this intermediate granulating process, granulation on the filter isperformed and the granules, which grew into granules of a particle sizeof 40 to 50 μm as a result of that granulation, come to form a fluidizedbed under a layer of secondary particles which have been made to fly up.Also, as the mist advancing air from the binder nozzle 9 is intensifiedto make the binder mist reach the fluidized bed, fluidized bedgranulation also starts to occur at the same time, making the granulesspherical.

Namely, the inside of the main body container is now in a stratifiedstate having a secondary particle layer, a primary granule layer andsecondary granule layer from top to bottom in this order. Granulation onthe filter is performed at the upper secondary particle layer, and thetop of the primary granule layer while fluidized bed granulation takesplace at the bottom of the primary granule layer and in the lowersecondary granule layer.

As this apparatus is a top spray type, a lot of binder mist is consumedin the secondary particle layer at the top where quick granulation isdesired, but only a small amount of binder mist reaches the secondarygranule layer at the bottom. For that reason, drying and pulverizationalso take place at the same time in the secondary granule layer at thebottom.

Namely, as secondary particles are actively granulated in the top layerwhile generated granules are slowly pulverized due to weaker bindingforces in the bottom layer, the granulation process progresses whileadjusting the particle size as a result.

FIG. 8 is a schematic diagram showing the regular granulating process ofpowder in the granulating step V.

In the regular granulating process of powder in the granulating step Vshown in FIG. 8, the granulation of the powder progresses and thesecondary particle layer disappears. Then, the binder mist, which has sofar been consumed in this layer, comes to be fully supplied to thefluidized bed, and the granules which grew into powder of a particlesize of 80 μm or so are rapidly granulated by fluidized bed granulation.However, there is something different from ordinary fluidized bedgranulation. The differences mean that the granules are comparativelydry because they formed in a dry zone in the bottom layer up to thegranulating step IV. In addition, the granules are wetted only on thesurface in this process, thereby keeping large granules hard, and smallgranules which became soft with wetting are combined with those largehard granules. Therefore, as the sprayed amount of binder mist is setwithin the drying capacity of hot air, granulation progresses in a stateof low water content and part of the granules are pulverized.

However, since granulation on the filter is possible also in the regulargranulating process, the powder which flew up after pulverization issubjected to granulation on filter and returned into the fluidized bedas easily granulated flaky granules wet with binder. Such a mechanismprovides granules of uniform particle size. Moreover, as granules ofloose binding force are pulverized and granulated again, this eventuallyproduces granules with a strong binding force.

Next, the process of growth of particles produced in the processes frominitial granulation to regular granulation described above isschematically indicated in FIG. 9.

In FIG. 9, a thick line indicates portions coated with binder, while adotted line represents portions in which the coated binder has dried up.

Such are the purpose by processes of granulation and the sequence ofactions. Their qualitative effects will be enumerated hereafter.

(1) By granulating on the filter, all of the powder is granulated afterbeing collected, forming a high-density powder layer on the filter 3. Asa result, there remains no ungranulated powder and the distribution ofparticle size is normalized.

(2) A combination of granulation on the filter and fluidized bedgranulation enables granulation in a state of low water content in thefluidized bed at the bottom. This prevents production of coarse grainsand normalizes the distribution of particle size.

(3) All processes are performed in a state of low water content with noproduction of false granules (granules without crosslinkage, which aresolidified lumps produced with moisture), providing granules of strongbinding force. Hence there is little pulverization in the dryingprocess.

(4) The granules, which are produced by coating the binder on each ofthe individual particles, are strong and easy to melt.

(5) In the case where granulation on the filter and fluidized bedgranulation are combined and put in the state of intermediate period ofgranulation, granules of uniform composition are obtained even withseveral different kinds of powder which are liable to be classified,because priority is given to the powder with smaller particle size inthe granulation and the regular granulation process starts after thepowder gets in a state of even size not easily classified from oneanother.

Next, an apparatus for granulation on the filter with spray-dry functionfor implementation of the present invention will be explained hereafterwith reference to FIG. 10 and FIG. 11.

It is to be noted, however, that this apparatus is intended toillustrate the technical concept of the present invention and that thepresent invention is not restricted to this specific apparatus.

First, the apparatus illustrated in FIG. 10, which is different in shapefrom an ordinary fluidized bed granulating apparatus, is constructed bysplitting the main body container into an upper structure 1A and a lowerstructure 1B, and depressing a central part of the top face of the upperstructure 1A.

This construction makes it possible to maintain a constant distance fromthe binder nozzle 9 to the fluidized bed regardless of the apparatussize, and makes the sprayed binder mist reach the fluidized powder.

Moreover, since the distance between the top face of the main bodycontainer 1 and the fluidized bed is comparatively short, it alsobecomes possible to scrape down the powder adhering to the top face aspart of the granules hit against that top face during granulation evenin the case of granulation of highly adhesive powder.

Furthermore, a filter cloth 3 is disposed on the inner circumferentialface of the main body container 1. In this case, it is possible toincrease the filtration surface area by also disposing a filter cloth 3on the inner circumferential face of the inner cylinder formed bydepressing the top face of the upper structure 1A of the main bodycontainer 1.

The filter cloth 3 is constructed by three pieces of filter cloth havingshapes that are different from one another, namely a first filter clothwhich is divided into six zones, 31, 32a, 33a, 34a, 35a, 36a, disposedon a flat part of the top face of the upper structure 1A of the mainbody container 1 and on the inner circumferential face of the outercylinder, a second filter cloth which is divided into five zones, 32b,33b, 34b, 35b, 36b, disposed on the inner circumferential face of theinner cylinder formed by depressing the top face of the upper structure1A of the main body container 1, and a third filter cloth which isdivided into two zones, 37, 38, disposed on the inner circumferentialface of the lower structure 1B of the main body container 1.

Further filter 3 is constructed in such a way as to allow the passage ofair, etc. but to prevent the passage of light fine powder. Namely, it isa double-layer structure having an inner filter 3A of woven fabric ofTetoron disposed on the inner side (center side of the main bodycontainer 1) and an outer filter 3B of fine mesh non-woven fabric ofTetoron.

Moreover, the filter 3 is formed in a flat shape in order to facilitatepeeling of a powder layer adhering to its surface.

In addition, filter 3 is divided into a plurality of zones by wall laand partition rings 1b of the main body container 1. In this case, therespective zones are arranged in a way to keep the surface areas of thefilter approximately uniform.

In the apparatus indicated in FIG. 10 and FIG. 11, the filter 3 isdivided into 8 zones, but the number of zones may be set depending onthe size of the apparatus.

Also, to make it possible to independently backwash the filter dividedinto zones, exhaust chamber 8 is provided on the back face in each zone,and the exhaust chamber 8 in the respective zones is connected to theexhaust header 40b through exhaust valve 40a of the exhaust mechanism 4and to the pressure tank for backwashing 50b through backwash valve 50aof the backwash mechanism 5 respectively.

The filter portion 31 is specified as zone 8a, filter portions 32a, 32bas zone 8b, filter portions 33a, 33b as zone 8c, filter portions 34a,34b as zone 8d, ditto 35a, 35b as zone 8e, ditto 36a, 36b as zone 8f,ditto 37 as zone 8g, and the filter 38 as zone 8h. The filter portionsfrom zone 8a to zone 8f function mainly as exhaust filters duringgranulation.

On the other hand, the filter in zones 8g, 8h positioned in the lowerpart is used for granulation on filter. For that reason, zones 8g, 8hmust be backwashed more frequently than other zones.

Moreover, in the case of granulation of powder which is liable to damagethe filter for example, fluidized bed granulation may be made by using alower structure formed of stainless steel without filters in place ofthe lower structure 1B which include filter forming zones 8g, 8h.

Next, the state of the filter 3 during operation will be explained withreference to FIG. 11.

FIG. 11 schematically indicates the moment when the backwash valve 50ain zone 8e opens to perform a backwashing operation.

Here, the filter in zones 8a, 8b, 8c, 8d, 8f is sucked and held to theexhaust chamber 8 side by the fluidizing air flow passing from insidethe main body container 1 to the exhaust header 40b through the exhaustchamber 8.

Also, the filters 35a, 35b in zone 8e instantly swell inward due to thebackwashing air flowing from the pressure tank 50b for backwashing intothe main body container 1 through the exhaust chamber 8. At that time,the powder layer formed on the filter 3 is peeled off of filter 3 andbroken into pieces.

To explain the actions of the exhaust valves and the backwash valves inthis case, backwashing is performed first by closing the exhaust valve40a in zone 8e and momentarily opening the backwash valve 50a from thestate in which all exhaust valves 40a are open and all backwash valves50a are closed.

When this backwash valve 50a in zone 8e is opened, the outer filter 3bis drawn into close contact with all partition rings 1c and fastened bythe filter presser ring 1d to prevent the backwashing air from leakingto the exhaust chamber 8 in zones 8d, 8f, while on the other hand theinner filter 3a is fastened to the partition ring 1c only at both endsof the first filters 31, 32a, 33a, 34a, 35a, 36a, second filters 32b,33b, 34b, 35b, 36b and third filters 37, 38, because too many fasteningpoints may cause accumulation of powder.

Next, explanation will be made on other constituent parts of theapparatus shown in FIG. 10.

This apparatus is provided, as in an ordinary fluidized bed granulatingapparatus, with the product container 10, screen plate 6, bottom airsupplying chamber 7 and lifting device 11.

Moreover, this apparatus is also provided with a top air supplyingchamber 2, which is used for the purpose of supplying hot air whenperforming spray-dry by using spray-dry nozzle 9 a in place of bindernozzle 9 by means of automatic nozzle replacing device 12.

The hot air flow which enters into this top air supplying chamber 2 isrectified by passing through a rectifying plate, etc. installed insidethe top air supplying chamber 2, and is supplied from the central partof the upper structure 1A into the main body container 1.

Furthermore, the hot air is used for the purpose of preventing, duringgranulation, adhesion of powder to the central part on the top face ofthe main body container 1 which is not covered by the filter 3.

At this time, the hot air flows fast along the top face of the main bodycontainer 1 by being dragged into the flow of the compressed airdischarged from the slits provided around the binder nozzle 9.

Next, an embodiment will be shown in which light fine powder wasmanufactured by the spray-dry method and then granulated in successionwithout removing the powder from the product container, by using theapparatus for granulating on the filter with spray-dry function.

Manufacturing process of light fine powder

In the light fine powder manufacturing process, a spray-dry nozzle, of2-fluid system capable of atomizing liquid into fine mist was used.Also, a solution for spray-dry prepared by dissolving a bulk ofantimetabolite in an organic solvent was sprayed into the main bodycontainer from the spray-dry nozzle and, in parallel with it, hot airfor drying was supplied from the top part of the main body container.The fine particles sprayed from the nozzle for spray-dry were put incontact with the hot air supplied from the top part of the main bodycontainer while running together with it, dried and turned into lightfine powder. That light fine powder rode on the fluidizing air flow, wasseparated from the air flow by the filter disposed on the face of themain body container, and only the light fine powder was caught on thefilter.

The light fine powder caught on the filter, the particle size of whichis as small as several μm, drops in the form of flocculated lumpscomposed of thousands of primary particles when it is peeled from thefilter. The lumps are collected in the product container at the bottomof the main body container. In this way, light fine powder composed offlocculated lumps of noncrystalline antimetabolite, the particle size ofprimary particles of which is several g m (hereinafter referred to as"flocculated powder"), was obtained.

As the conditions of spray-dry, the volume of hot air used for thedrying was set for 40 m³ /min, the supply air temperature at 65° C., theflow rate of spray-dry solution at 3.2 kg/min, the atomizing airpressure for pulverizing that solution at 5.0 kgf/cm², and the flow rateat 4.0 Nm³ /min.

As the backwash conditions, the backwash will be set in a way to beperformed sequentially from top to bottom. In that case, the backwashinterval is set for 15 seconds, the backwash time per point for 1 secondand the backwash air pressure at 5 kgf/cm².

Particle size distribution, mean particle diameter, bulk density andweight of the noncrystalline antimetabolite with a particle size ofseveral g m obtained by the method described above are shown in Table 1.

                                      TABLE 1                                     __________________________________________________________________________    Particle size distribution                                                    __________________________________________________________________________    Particle diameter [μm]                                                               17.75                                                                            12.55                                                                            8.87                                                                             6.27                                                                             4.43                                                                             3.13                                                                             2.21                                                                             1.30                                                                             0.80                                                                             0.55                                                                             0.39                                  wt %      0  3.6                                                                              11.8                                                                             18.9                                                                             19.3                                                                             14.5                                                                             12.1                                                                             9.7                                                                              6.1                                                                              4.0                                                                              0                                     __________________________________________________________________________     Mean particle diameter . . . 4.39 [μm                                      Bulk density . . . 0.243 [g/cc                                                Weight . . . 60 [kg                                                      

Granulation process of flocculated powder

To granulate the flocculated powder, the spray-dry nozzle which wasprovided at the top of the main body was replaced with a binder nozzle.

Also, fluidizing air was fed from the bottom air supplying chamber tothe flocculated powder collected in the product container, to blow upand fluidize the flocculated powder. The result is that the flocculatedpowder is somewhat pulverized with the mixing action made by utilizingthe filter to change into flocculated powder of smaller size.

Also, to prevent, the small flocculated powder from becoming flocculatedpowder of a larger size again, 900 g of light silicic acid anhydride wasadded as flocculation inhibitor, and was mixed sufficiently well untilfluidity appears in the powder. After that, vehicles (lactose 40 kg,microcrystalline cellulose 13.5 kg) were injected by sucking into thisfluidized flocculated powder by utilizing the presence of negativepressure inside the main body container.

When the injected vehicles and the flocculated powder were blendedsufficiently well, a small amount of binder was sprayed from the bindernozzle for the purpose of deflocculation.

After that, the feed volume of the binder was increased to performinitial granulation (the granulation on filter), and the feed volume ofthe mist advancing air from the binder nozzle was increased when thegranules which grew with granulation on the filter came to form afluidized bed so that the binder mist may reach the fluidized bed.

The granulation process to progressed in this way and, when the particlesize of the granules became the target size, the feed of the binder wasstopped for drying, and granulated products were obtained.

As the conditions of granulation, the volume of hot air used forfluidizing the mixed powder was set for 80 m³ /min, the supply airtemperature at 609 C., and the supply air humidity at 7 g/kg. As thebinder, 3% aqueous solution of hydroxy propylmethyl cellulose was used,and its flow rate was set for 560 g/min in the deflocculation processand 1050 g/min in the initial granulation (the granulation on thefilter), intermediate granulation (a combination of the granulation onthe filter and fluidized bed granulation) and regular granulation(fluidized bed granulation) processes, while the atomizing air flow ratewas set for 1500 NL/min.

In addition, the volume to feed the mist advancing air from the bindernozzle was set for 300 NL/min during the deflocculation process and theinitial granulation process but for 800 NL/min in the intermediategranulation process and the and regular granulation process.

The conditions of drying were the same as those of granulation as far asthe supply air volume, supply air temperature and supply air humiditywere concerned.

As for the backwash conditions, in order to backwash the filter 37,38,in the bottom stages, where granulation on the filter is made actively,more frequently than others, the backwash is performed by the followingsequence.

Namely, the backwash is made in the order of filter 31→37→32a,32b→38→33a, 33b→37→34a, 34b→38→35a, 35b→37→36a, 36b→38, with backwashinterval of 15 seconds, backwash time per point of 1 second and backwashair pressure of 5 kgf/cm².

The particle size distribution, content, yield, dissolution rate andwater content in granule of the granulated products obtained as a resultof this operation were as shown on Table 2

                                      TABLE 2                                     __________________________________________________________________________    Particle size distribution                                                    Mesh       30M 42M 60M 83M 140M                                                                              200M                                                                              PASS                                       __________________________________________________________________________    wt %       3.7 16.7                                                                              25.9                                                                              25.9                                                                              22.2                                                                              3.7 1.9                                                   100.32                                                                            101.56                                                                            98.68                                                                             101.74                                                                            99.88                                              Content [%]                                                                              101.50                                                                            99.67                                                                             99.74                                                                             100.04                                                                            100.49                                             (sampled at 20 points)                                                                   100.25                                                                            101.62                                                                            100.61                                                                            98.78                                                                             99.83                                                         100.38                                                                            99.56                                                                             100.48                                                                            99.72                                                                             101.63                                             __________________________________________________________________________     Mean content 100.324[%                                                        Standard deviation 0.911                                                      Process capability index 2.56                                                 (Case of 93-107% content standard)                                            Yield 98.5[%                                                                  Dissolution rate 94.3[%                                                       Water content in granule (before drying) 3.17[%                               Water content in granule (after drying) 1.93[%                           

Reference Example

Granulation was made under the conditions given below by using aconventional fluidized bed granulation apparatus with the same rawmaterial (noncrystalline antimetabolite of a particle size of 4.01 μm 12kg, lactose 8.0 kg, microcrystalline cellulose 2.7 kg) and the samebinder as those of the embodiment, and comparison was made with thegranulated products made by the embodiment on particle sizedistribution, content, yield, dissolution rate and water content ingranule. The raw material had been mixed in advance by using ahigh-speed mixer.

As the conditions of granulation and drying, the supply air temperaturewas set at 60° C., and the supply air humidity at 7 g/kg, and the volumeof hot air was set for 5 m³ /min during the period of 30 minutes fromthe start of granulation and for 15 m'/min thereafter up to the end ofgranulation and during the drying. The flow rate of the binder was setfor 200 g/min during the period from the start to the end ofgranulation.

Table 3 indicates the comparative data.

                                      TABLE 3                                     __________________________________________________________________________    Particle size distribution [wt %]                                             __________________________________________________________________________    Mesh           60M  42M  60M  83M  140M  200M  Pass                           __________________________________________________________________________    Embodiment:    3.7  16.7 25.9 25.9 22.2  3.7   1.9                            Granulation on the filter +                                                   Fluidized bed granulation                                                     Reference example:                                                                           20.8 23.3 16.9 11.7 9.6   8.2   9.5                            Fluidized bed granulation                                                     __________________________________________________________________________                           Process         Water content                                        Mean                                                                              Standard                                                                           capability                                                                              Dissolution                                                                         in granulate [%]                                     content                                                                           deviation                                                                          index                                                                              Yield [%]                                                                          rate [%]                                                                            Before drying                                                                        After drying                    __________________________________________________________________________    Embodiment:   100.324                                                                           0.911                                                                              2.56 98.5 94.3  3.17   1.93                            Granulation on the filter +                                                   Fluidized bed granulation                                                     Reference example:                                                                          94.12                                                                             2.54 0.92 86.4 80.2  13.5   2.2                             Fluidized bed granulation                                                     __________________________________________________________________________

Observations will be made hereafter on the comparative data indicated inTable 3.

In the embodiment, granulation on the filter was made in the lower partof the main body container and fluidized bed granulation was performedin the product container. As a result, granulated products of uniformparticle size were obtained because powder of small particle size isgranulated preferentially and that of larger size is pulverized in thedry zone by the granulation on the filter.

On the other hand, the conventional fluidized bed granulation method ofthe reference example consists in first spraying binder in a volumeapproximately 3 times the hot air drying capacity and performinggranulation in a state of high water content by increasing the watercontent of the light fine powder in a short time. For that reason,coarse particles of a diameter of 1 to 10 mm were produced in a largequantity. Moreover, the light fine powder, which flied up and adhered tothe filter and the inner circumferential face of the main body containerin the early period of granulation, dropped in non granulated stateafter the end of granulation at the time of collection of granulatedproducts, without falling during the granulation. For that reason, thesegranulated products came to contain a lot of coarse granules of 30-meshor over and fine powder of particle size of 200-mesh or under.

Furthermore, by the granulation on the filter method of the embodiment,there was no adhesion of light fine powder to the inner face of theapparatus and the yield improved, because the mixed powder which fliedup with fluidizing air flow in the early period of granulation isforcibly caught on the filter. And, the light fine powder which wasclassified with the fluidizing air flow was also mixed completely withthe progress of granulation, and the mean content was almost 100%.

On the other hand, by the conventional fluidized bed granulation methodof the reference example, the mean content dropped because much of thepowder which adhered to the inner face of the apparatus consisted ofhighly adhesive bulk of antimetabolite, in spite of the fact that theraw material had been mixed in advance. And, the yield also dropped to86.4% because of a lot of loss due to adhesion. In addition, there was alarge deviation of content because a lot of flocculated lumps drop innon granulated state from the filter at the time of collection ofgranulated products after the granulation, and this cannot be consideredas uniform content judging from the process capability index.

On the contrary, by the granulation on the filter method of theembodiment, there was little deviation of content and the processcapability index indicated values of 1.33 or over, and this may well beconsidered as uniform content.

In addition, the granulated products of the embodiment, which underwenta deflocculation process, indicated a better dissolution rate in thestabilizing test compared with the granulated products of the referenceexample which did not undergo any deflocculation.

Next, to compare the quality of the granulated products obtained by theembodiment and the reference example, those granulated products wereprocessed into tablets by using one same apparatus (tablet machine) andunder one same condition (tablet making pressure 1200 kg) and thehardness and the dissolution rate of the tablets obtained were measured.Table 4 indicates the results of measurements. The hardness value givenhere is the mean value of the measured values of 10 tablets picked up atrandom.

                  TABLE 4                                                         ______________________________________                                        Hardness and dissolution rate of tablets                                                     Hardness [kp]                                                                          Dissolution [%]                                       ______________________________________                                        Embodiment       12.1       94.6                                              (with deflocculation process)                                                 Reference example                                                                              8.4        73.3                                              (without deflocculation process)                                              ______________________________________                                    

Observations will be made hereafter of the comparative data given inTable 4.

The higher the hardness of tablets, the better the tablets, because theyare less liable to be destroyed or worn in the distribution process orduring the use. Moreover, the higher the dissolution rate, the better,because the tablets must fully dissolve in the prescribed time. However,the general trend is that as the hardness is increased the dissolutionrate gradually drops.

Nevertheless, the tablets of the embodiment presented higher hardnessand higher dissolution rate compared with those of the reference examplein spite of the fact that both of them were produced under one samecondition. Namely, the dissolution rate of the tablets of the embodimentdid not drop in spite of an increased hardness.

This comes from the difference of granulated products. The granulatedproducts of the embodiment were coated with a binder on all primaryparticles in the deflocculation process. For that reason, the binder onthe surface of the primary particles played the roll of an adhesive andbonded all primary particles at the time of tablet making, and thisresulted in high hardness of tablets. Moreover, the dissolution rate ofthese tablets did not drop because the binder on the surface of theprimary particles is easily melted and dispersed to the individualprimary particles. On the contrary, the granulated products of thereference example are not coated with the binder on the primaryparticles inside the flocculated lump, because they were granulated byjust spraying a large flow rate of binder, without making anydeflocculation, to coat the binder in a way to cover the surface of theflocculated lumps and bind those flocculated lumps to one another. Forthat reason, the tablets made of those granulated products becamefragile at the inside of the flocculated lumps where there is no binderand their hardness dropped. Furthermore, since those tablets weresubmitted to mechanical pressure, at the time of tablet making, in thestate without binder on the surface of the primary particles inside theflocculated lumps, the primary particles inside the flocculated lumpswere fixed without being dispersed to the individual primary particlesat the time of dissolution, leading to a low dissolution rate.

We claim:
 1. A method of granulating powder, said methodcomprising:mixing a powder of primary particles and a mist of binder bymeans of a fluidizing air flow in a main body container so as to form amixture; collecting the mixture of the powder and the binder on a filtersurface of a filter, which is disposed in a generally flat shape in sucha way as to cover an inner circumferential face of the main bodycontainer, such that a powder layer of primary particles is formed onthe filter surface; peeling the powder layer off from the filter surfaceso as to crush the powder layer into fragments; returning the fragmentsinto the fluidizing air flow and mixing the fragments with the bindermist again; and repeating the above steps until the binder is coated onall of the primary particles and a desired granule of coated primaryparticles is obtained.
 2. The method claimed in claim 1, furthercomprising:flocculating a large number of primary powder particles inorder to form flocculated lumps; spotting the binder on a surface of theflocculated lumps; collecting the flocculated lumps on the filtersurface with the fluidizing air flow; combining only coated portions ofthe primary particles in a high-density powder layer which issubsequently broken away from a powder portion, which is not combinedwith the binder, by backwashing; and repeating the above operations inorder to loosen the first flocculated lumps and to coat the individualprimary particles of the lumps with the binder.